The metabolic basis and pathogenesis of a new caprine inherited neurological disease will be investigated. Affected newborn progeny of related Anglo-Nubian goats demonstrate severe neurological deficits accompanied by neuronal vacuolation, axonal dystrophy and diminution of myelin. Pilot studies revealed possible storage and urinary excretion of mannose and N-acetyl glucosamine-enriched oligosaccharides. Further analysis of major accumulated oligosaccharides indicated that the storage material is a trisaccharide with the tentative structure of Man (beta1 yields 4)GlcNAc(beta1 yields 4)GlcNAc(beta1 yields ?). This suggests that the disorder may be a beta-D-mannosidase deficiency since the accumulated trisaccharide contains one of the only known beta-mannose structures, the common core structure of N-linked glycopeptides. Preliminary analysis of liver lysosome beta-D-mannosidase indicated a greatly diminished activity in liver of affected goats as compared to normals and a partially reduced activity in heterozygotes. Characterization of the accumulated oligosaccharides in brain will be performed by methylation analysis and by degradation studies. More complex oligosaccharides in urine, observed in preliminary thin layer chromatograms of affected goats, will be characterized to determine whether they result from accumulation of unknown beta-mannose containing saccharides or whether they are normal glycopeptides excreted by the pathological kidney. Brain and liver beta-D-mannosidase will be partially purified by DEAE cellulose chromatography and by gel filtration of normal and affected goat tissues. The yield of active enzyme will be quantified by incubation with paranitrophenyl beta-D-mannoside or beta-mannosyl chitobiose isolated from serum glycoproteins and other sources. The extent to which the various tissues of the affected goat lack the enzyme, accumulate metabolic products and demonstrate pathological alterations will be assessed to clarify the pathogenesis of this inherited lethal disease.